Amlodipine with Clarithromycin Interaction Details

Brand Names Associated with Amlodipine

Brand Names Associated with Clarithromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 03, 2024

Interaction Effect

Increased risk of hypotension, acute kidney injury, bradyarrhythmias, lactic acidosis and peripheral edema

Interaction Summary

Coadministration of clarithromycin (a strong CYP3A4 inhibitor) and calcium channel blockers (CCBs) metabolized by CYP3A4 has resulted in serious adverse effects including hypotension and acute kidney injury[1][2]. Additionally, concomitant administration may also cause bradyarrhythmias, lactic acidosis, and peripheral edema [2]. Use caution with concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 [1][2]. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required [3].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of clarithromycin (a strong CYP3A4 inhibitor) and calcium channel blockers metabolized by CYP3A4 has resulted in serious adverse effects including hypotension and acute kidney injury[1][2]. Additionally, concomitant administration may also cause bradyarrhythmias, lactic acidosis, and peripheral edema [2].Use caution with concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 [1][2]. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required [3].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism by clarithromycin

Literature Reports

A) Coadministration of macrolide antibiotics erythromycin or clarithromycin with a calcium channel blocker was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock ([OR, 5.8; 95% CI, 2.25 to 14.98] or [OR, 3.7; 95% CI, 2.26 to 6.06]) in a case-crossover cohort study of geriatric patients (N=7100); there was no significant risk associated with azithromycin. In a stratified analysis of dihydropyridine calcium channel blockers (amLODIPine, felodipine, NIFEdipine), the results remained significant for coadministration of erythromycin or clarithromycin. Calcium channel blocker treatment included dilTIAZem (40%), amLODIPine (29.6%), NIFEdipine (19.4%), verapamil (8%), or felodipine (3%). The findings suggest that erythromycin and clarithromycin potentiate calcium channel blockers (CYP3A4 substrates) by inhibiting CYP3A4; azithromycin does not inhibit CYP3A4 [3].

B) Relative to azithromycin, clarithromycin was associated with a small but significant 30-day increased risk of hospitalization with acute kidney injury (HAKI) in patients who received continuous calcium channel blocker (CCB) therapy in a retrospective cohort of older adults (mean age, 76 years). Of the patients receiving clarithromycin, CCB usage included: amLODIPine (52.7%), dilTIAZem (22.2%), NIFEdipine (17.3%), verapamil (4%), or felodipine (3.8%). The median dose of clarithromycin was 1000 mg/day for 10 days (n=96,226) and the median dose of azithromycin was 300 mg/day for 5 days (n=94,083). Pooled data was analyzed, 30 days after the antibiotic was prescribed, for diagnostic code of HAKI (median absolute acute increase in serum creatinine of 1.11 mg/dL). HAKI occurred in 0.44% of patients prescribed clarithromycin compared with 0.22% of patients prescribed azithromycin (odds ratio [OR], 1.98; 95% CI, 1.68 to 2.34; number needed to harm (NNH), 464). Relative to amLODIPine (reference), the risk of HAKI was highest with NIFEdipine, followed by felodipine, dilTIAZem, and verapamil. Similarly, concomitant use of clarithromycin in CCB recipients was associated with a small but significant 30-day increased risk of hospitalization with hypotension (absolute risk increase, 0.04%) and all-cause mortality (absolute risk increase, 0.43%). Risk of HAKI appeared unaffected by presence of chronic kidney disease (CKD) or statin use; however, NNH decreased to 95 in those with CKD. Additional multiple analyses showed similar results, suggesting robustness of findings [4].

C) In elderly hypertensive patients, coadministration of amLODIPine 5 mg with dilTIAZem (a moderate CYP3A4 inhibitor) 180 mg daily resulted in a 60% increase in amlodipine exposure [5].

References

1 ) Product Information: BIAXIN(R) XL Filmtab(R) oral extended-release tablets, clarithromycin oral extended-release tablets. AbbVie Inc (per FDA), North Chicago, IL, 2018.

2 ) Product Information: VOQUEZNA(TM) TRIPLE PAK(TM) oral kit, vonoprazan oral tablets, amoxicillin oral capsules, clarithromycin oral tablets kit. Phathom Pharmaceuticals (per FDA), Buffalo Grove, IL, 2023.

3 ) Wright AJ, Gomes T, Mamdani MM, et al: The risk of hypotension following co-prescription of macrolide antibiotics and calcium-channel blockers. CMAJ 2011; 183(3):303-307.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Gandhi S, Fleet JL, Bailey DG, et al: Calcium-channel blocker–clarithromycin drug interactions and acute kidney injury. JAMA 2013; 310(23):2544-2553.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

5 ) Product Information: NORVASC(R) oral tablets, amlodipine besylate oral tablets. Pfizer Labs (per FDA), New York, NY, 2013.

Amlodipine Overview

• Amlodipine is used alone or in combination with other medications to treat high blood pressure in adults and children 6 years and older. It is also used to treat certain types of angina (chest pain) and coronary artery disease (narrowing of the blood vessels that supply blood to the heart). Amlodipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood to the heart. If taken regularly, amlodipine controls chest pain, but it does not stop chest pain once it starts. Your doctor may prescribe a different medication to take when you have chest pain.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.